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This isn't speculation

A lactam bridge loaded at Glu 22 , either c[Lys 18 Glu 22 ] or c[Glu 22 Lys 26 ], shows lower affinity and activity than a simple substitution of Gly 22 with Glu

This review explores tirzepatide's mechanisms of action, clinical efficacy, and safety profile, with particular attention to its impact on T2DM, obesity, cardiovascular health, metabolic-associated fatty liver disease (MAFLD), chronic kidney disease (CKD), and neurological disorders such as Alzheimer's and Parkinson's diseases

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[1] [3] Clinical trials, including the SURMOUNT and SURPASS programmes, have demonstrated significant weight loss that varies by dose and populationin the SURMOUNT-1 trial of non-diabetic adults, mean weight loss ranged from approximately 15% (5 mg dose) to 20% (15 mg dose) after 72 weeks